IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging
IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging
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DOI：
10.1016/j.neulet.2015.05.019
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发表时间：
2015-07
影响因子：
2.5
通讯作者：
C. Wakabayashi;T. Numakawa;Haruki Odaka;Yoshiko Ooshima;Y. Kiyama;T. Manabe;H. Kunugi;Y. Iwakura
中科院分区：
文献类型：
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作者：
C. Wakabayashi;T. Numakawa;Haruki Odaka;Yoshiko Ooshima;Y. Kiyama;T. Manabe;H. Kunugi;Y. Iwakura
白介素1(IL-1)在应激反应中起关键作用，其mRNA在大脑中由束缚应激诱导。此前，我们报道了IL-1受体拮抗剂(IL-1ra)基因敲除(KO)小鼠在8周龄时通过肾上腺素能调节表现出抗抑郁行为。在这里，我们报告了IL-1Ra KO小鼠在高架正迷宫(EPM)测试中表现出的焦虑样表型，这种表型是由衰老自发诱导的。这种焦虑样的表型可以通过安定的治疗得到改善。与野生型(WT)小鼠相比，焦虑相关分子糖皮质激素受体(GR)在20周龄的IL-1Ra KO小鼠中的表达显著减少，但在11周龄的IL-1Ra KO小鼠中的表达不明显。IL-1Ra KO小鼠和WT仔鼠在11周龄和20周龄时，盐皮质激素受体(MR)的表达没有改变。海马单胺浓度分析显示，20周龄IL-1Ra KO小鼠的色氨酸、5-羟色胺代谢产物5-羟基吲哚乙酸(5-HIAA)和多巴胺代谢产物高香草酸(HVA)较产仔WT小鼠显著增加。这些发现有力地表明，在老年小鼠中观察到的焦虑样行为是由海马单胺代谢和/或GR表达的复杂变化引起的。
Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus.